SignificanceStandard treatments for isolated lung metastases remain a clinical challenge. In vivo lung perfusion technique provides flexibility to overcome the limitations of photodynamic therapy (PDT) by replacing the blood with acellular perfusate, allowing greater light penetration.AimUsing Monte Carlo-based simulations, we will evaluate the abilities of a light delivery system to irradiate the lung homogenously. Afterward, we aim to demonstrate the feasibility and safety profile of a whole-lung perfusion-assisted PDT protocol using 5-ALA and Chlorin e6.ApproachA porcine model of a simplified lung perfusion procedure was used. PDT was performed at 630 or 660 nm with 5-ALA or Chlorin e6, respectively. Light fluence rate measurements and computed tomography (CT) scan segmentations were used to create in silico models of light propagation. Physiologic, gross, CT, and histological assessment of lung toxicity was performed 72 h post-PDT.ResultsDose-volume histograms showed homogeneity of light intensity throughout the lung. Predicted and measured fluence rates showed strong reliability. The photodynamic threshold of 5-ALA was 2.10×1017±8.24×1016 hν/cm3, whereas Chlorin e6 showed negligible uptake in lung tissue.ConclusionsWe lay the groundwork for personalized preoperative in silico dosimetry planning to achieve desired treatment volumes within the therapeutic range. Chlorin e6 demonstrated the greatest therapeutic potential, with a minimal uptake in healthy lung tissues.
KEYWORDS: Photodynamic therapy, Pancreas, Tissue optics, Monte Carlo methods, Arteries, Tissues, In vivo imaging, Prototyping, Image segmentation, Computed tomography
Patients with pancreatic adenocarcinoma have a short survival time and many are not eligible for surgery due to vascular proximity or involvement. Hence, downstaging therapies that can effectively clear the tumor from the vessel, are desirable. We hypothesize photodynamic ablation via the endovascular route can effectively clear vessels from such tumor involvement.
To evaluate endovascular light delivery for Photodynamic therapy (PDT) as a potential approach, proof-of-concept studies were performed, including in silico Monte Carlo light simulations, and in vivo, testing in a porcine model. Monte Carlo simulations were carried out in an anatomic realistic model based on segmentation of a porcine pancreas and its blood vessels, where light sources were placed into the superior mesenteric and splenic arteries. Tissue response was evaluated based on the photodynamic threshold model taking local fluence, photosensitizer and tissue sensitivity into consideration. The simulations showed that while limiting the irradiance on the intima to non-thermal levels, pancreatic tissue destruction up to several mm is feasible within clinically acceptable irradiance times for BPD-MA mediated PDT. In vivo studies used normal pigs where pre-and-post PDT contrast-enhanced CT scans (24-48h) were performed to obtain anatomical details and to evaluate gross tissue response. The splenic, hepatic and superior mesenteric arteries were reached via the femoral access route. A guidewire was inserted under fluoroscopy and exchanged with a prototype endovascular catheter for intravascular irradiation. We found it feasible to reach the target areas, however optimal positioning of the irradiators within the prototype catheter was somewhat challenging. Light delivery of several hundreds of J.cm-2 is feasible albeit requiring long irradiation and vessel occlusion times. No vessel perforations were noted on histopathology, however some expected necrosis in smooth muscle cells. The maximum radius of necrosis beyond the vessel's outer diameter reached several mm. This is potentially acceptable for downstaging patients and performing surgical tumor resection.
Significance: Open-source software packages have been extensively used in the past three decades in medical imaging and diagnostics, aiming to study the feasibility of the application ex vivo. Unfortunately, most of the existing open-source tools require some software engineering background to install the prerequisite libraries, choose a suitable computational platform, and combine several software tools to address different applications.
Aim: To facilitate the use of open-source software in medical applications, enabling computational studies of treatment outcomes prior to the complex in-vivo setting.
Approach: FullMonteWeb, an open-source, user-friendly web-based software with a graphical user interface for interstitial photodynamic therapy (iPDT) modeling, visualization, and optimization, is introduced. The software can perform Monte Carlo simulations of light propagation in biological tissues, along with iPDT plan optimization. FullMonteWeb installs and runs the required software and libraries on Amazon Web Services (AWS), allowing scalable computing without complex set up.
Results: FullMonteWeb allows simulation of large and small problems on the most appropriate compute hardware, enabling cost improvements of 10 × versus always running on a single platform. Case studies in optical property estimation and diffuser placement optimization highlight FullMonteWeb’s versatility.
Conclusion: The FullMonte open source suite enables easier and more cost-effective in-silico studies for iPDT.
Based on CARS-SHG spectroscopy biomolecular fingerprints of lipids/proteins were distinguished in isolated adult cardiomyocytes of α-Gal-A-Knockout and wild-type mice opening new prospects for diagnostic of cardiac manifestations of Morbus Fabry.
Access to the requested content is limited to institutions that have purchased or subscribe to SPIE eBooks.
You are receiving this notice because your organization may not have SPIE eBooks access.*
*Shibboleth/Open Athens users─please
sign in
to access your institution's subscriptions.
To obtain this item, you may purchase the complete book in print or electronic format on
SPIE.org.
INSTITUTIONAL Select your institution to access the SPIE Digital Library.
PERSONAL Sign in with your SPIE account to access your personal subscriptions or to use specific features such as save to my library, sign up for alerts, save searches, etc.